Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA; Indiana University Center for Aging Research, Regenstrief Institute, Indianapolis, Indiana, USA; Indiana University Center of Health Innovation and Implementation Science, Indianapolis, Indiana, USA.
Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Heart Lung. 2024 Jan-Feb;63:35-41. doi: 10.1016/j.hrtlng.2023.09.009. Epub 2023 Sep 23.
Postoperative delirium occurs in up to 80% of patients undergoing esophagectomy. We performed an exploratory proteomic analysis to identify protein pathways that may be associated with delirium post-esophagectomy.
Identify proteins associated with delirium and delirium severity in a younger and higher-risk surgical population.
We performed a case-control study using blood samples collected from patients enrolled in a negative, randomized, double-blind clinical trial. English speaking adults aged 18 years or older, undergoing esophagectomy, who had blood samples obtained were included. Cases were defined by a positive delirium screen after surgery while controls were patients with negative delirium assessments. Delirium was assessed using Richmond Agitation Sedation Scale and Confusion Assessment Method for the Intensive Care Unit, and delirium severity was assessed by Delirium Rating Scale-Revised-98. Blood samples were collected pre-operatively and on post-operative day 1, and discovery proteomic analysis was performed. Between-group differences in median abundance ratios were reported using Wilcoxon-Mann-Whitney Odds (WMWodds) test.
52 (26 cases, 26 controls) patients were included in the study with a mean age of 64 (SD 9.6) years, 1.9% were females and 25% were African American. The median duration of delirium was 1 day (IQR: 1-2), and the median delirium/coma duration was 2.5 days (IQR: 2-4). Two proteins with greater relative abundance ratio in patients with delirium were: Coagulation factor IX (WMWodds: 1.89 95%CI: 1.0-4.2) and mannosyl-oligosaccharide 1,2-alpha-mannosidase (WMWodds: 2.4 95%CI: 1.03-9.9). Protein abundance ratios associated with mean delirium severity at postoperative day 1 were Complement C2 (Spearman r = -0.31, 95%CI [-0.55, -0.02]) and Mannosyl-oligosaccharide 1,2-alpha-mannosidase (r = 0.61, 95%CI = [0.29, 0.81]).
We identified changes in proteins associated with coagulation, inflammation, and protein handling; larger, follow-up studies are needed to confirm our hypothesis-generating findings.
接受食管切除术的患者中多达 80%会发生术后谵妄。我们进行了一项探索性蛋白质组学分析，以确定可能与术后谵妄相关的蛋白质途径。
在年轻且风险较高的手术人群中，确定与谵妄和谵妄严重程度相关的蛋白质。
我们使用从参加阴性、随机、双盲临床试验的患者中采集的血液样本进行了病例对照研究。纳入标准为年龄在 18 岁或以上、接受食管切除术且采集血液样本的英语患者。病例组定义为手术后出现阳性谵妄筛查，而对照组为无谵妄评估的患者。使用 Richmond 激越镇静量表和重症监护病房意识模糊评估法评估谵妄，使用修订后的 98 项谵妄评定量表评估谵妄严重程度。采集患者术前和术后第 1 天的血液样本，并进行发现性蛋白质组学分析。采用 Wilcoxon-Mann-Whitney Odds (WMWodds) 检验报告组间中位数丰度比的差异。
52 例（26 例病例，26 例对照）患者纳入研究，平均年龄为 64（SD 9.6）岁，1.9%为女性，25%为非裔美国人。谵妄持续时间中位数为 1 天（IQR：1-2），谵妄/昏迷持续时间中位数为 2.5 天（IQR：2-4）。在谵妄患者中相对丰度比更高的两种蛋白质是：凝血因子 IX（WMWodds：1.89 95%CI：1.0-4.2）和甘露糖寡糖 1,2-α-甘露糖苷酶（WMWodds：2.4 95%CI：1.03-9.9）。与术后第 1 天平均谵妄严重程度相关的蛋白质丰度比为补体 C2（Spearman r=-0.31，95%CI[-0.55，-0.02]）和甘露糖寡糖 1,2-α-甘露糖苷酶（r=0.61，95%CI= [0.29，0.81]）。
我们确定了与凝血、炎症和蛋白质处理相关的蛋白质变化；需要更大规模的随访研究来证实我们的假设生成结果。
